Dr Phillips on the Evolution of BTK Inhibitors in MCL

Tycel Phillips, MD, hematologist-oncologist, associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the evolution of treatment with BTK inhibitors for patients with mantle cell lymphoma (MCL).

The evolution of MCL treatment has largely been driven by BTK inhibitors, he begins. Historically, 3 covalent BTK inhibitors have impacted the paradigm: ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa). However, the indication of ibrutinib for patients with MCL who have received at least 1 prior therapy was voluntarily withdrawn from the United States market following results from the phase 3 SHINE study (NCT01776840) in elderly patients, Phillips reports. As a result of this decision, 2 second-generation covalent BTK inhibitors remain for pretreated patients with MCL: zanubrutinib and acalabrutinib. However, there is ongoing effort to push these drugs into frontline setting, rather than limiting them to second-line treatment where they have traditionally been used as the standard of care, he elucidates.

As these drugs are moved forward in the treatment paradigm, a key question is whether they can be used in an abbreviated treatment approach, administered for a short period before stopping, Phillips explains. There is currently a lack of data on how patients will respond when rechallenged with these drugs after a break, according to Phillips. Specifically, it is unclear whether the duration of response will be the same as before, or if continuous and intermittent treatment will yield similar outcomes, he states.

Additionally, there is the issue of treating patients who progress on BTK inhibitors, Phillips expands. Historically, few drugs have been effective after patients progress on BTK inhibitors, which complicates treatment options in the third-line setting and beyond, Phillips says. This limitation underscores the need for new strategies and therapies to address this challenge, he says. Overall, despite advancements in the use of BTK inhibitors, there are still many uncertainties; addressing these questions is crucial for improving outcomes in this patient population, Phillips concludes.